Week 4 Worksheet (2025)

Asal Ardalan Study Guide - PHAR 840 (Farris) Spring 2025 Upon completion of this exercise, you will be able to: Immunomodulatory Agents 1. Distinguish between the functions and mechanisms of the Innate and Adaptive Immune Systems Innate is always present and activated and ready to go. Has no memory and it tails off. Adaptive immunity requires the system to be activated by binding the b cell or t cell to the antigen or compartment antigen (priming). Has a memory. If the body see the antigen previously, it often times will react rapidly to that antigen without having to take a long time to develop the adaptive system 2. Identify the cells derived from Lymphoid and Myeloid lineage. 3 cells drives form lymphoid lineage (Natural killer cell, B cells , T cells). Everything else comes from myeloid lineage 3. Identify the primary functions of B and T lymphocytes B cells : primary function is making antibodies T cells: we have 3 primary class of T cells. T helper cells (They help the other cytotoxic T cells or they may help B cells. They don’t necessary act directly on something. Cytotoxic T cells, directly act on a pathogen to destroy it. Regulatory T cells are associated with memory and regulatory functions. T cells are more diverse in terms of functions 4. Describe the structure and function of antibodies Fc region if it’s bound to the cell membrane that segment is bound to the membrane. A lot of biological characteristics are from FC region. 5. Identify the heavy chain proteins that define the different classes of antibodies 6. Define Antigen Any agent or molecule that can stimulate an immune response by the body Asal Ardalan 7. Name the two types of molecular complexes that recognize antigens Immunoglobulins of the B cells ( B cell receptor or the antibodies) and T cell antigen receptors 8. Recognize which type of T-Lymphocyte is associated with the presence of CD4, CD8, CD4+CD25, and CD8+CD25 9. Define Cytokine More proteins that are secreted by lymphocytes or some cases are cells as well. Have some sort of effect on communication or interaction of immune cells. They have kind of effects that hormones might have. Interleukins: Primary glycoproteins. Interlukins-2 : drives from T cells and act on T cells and natural killer cells . Primary function of Interleukins 2 is propagate proliferations and inducing the activity of T cell 10. Characterize the four most important classes of cytokines -same as #9 11. Explain how presentation of antigens to T-Lymphocytes differs from antigen presentation to BLymphocytes B lymphocytes can bind to antigen directly. T cells have to antigen presented to them by antigen presenting cells displayed on a major histocompleclecitbly complex or hemolymphoctes antigen region of that antigen presenting cell 12. Name the region of the Antigen Presenting Cell (APC) that is responsible for presenting the antigen to T-lymphocytes MAC ( major histocompatibility complex) or sometimes it calls human lymphocyte antigen (HLA) 13. Name the CDs on both the APC and the cytotoxic T-Lymphocyte that are responsible for costimulation Primary stimulatory interaction is between the MAC and T cell receptor. Costimulatory is between CD80 and CD86 on the antigen presenting cell and the CD28 on the T cell 14. Describe the finctional importance of Calcineurin( Important ) Is a phosphatase (phosphorylates molecules). For example it can phosphorylate the cytophorm of the NFAT and calcineurin dephosphorylate the NFAT so it can enter the nucleus and act as the transcription factor to produce bunch of cytokines including IL-2 15. Describe the importance of IL-2 to cytotoxic T-cell development Asal Ardalan IL-2 binds to IL-2 receptor then IL-2R propagates or stimulates a transduction cycle that goes through series and intermediates and ultimately assists in a propagation and maturation of the T cell 16. Differentiate Signal 1 (primary) and Signal 2 (secondary) that occur between APC and TLymphocytes 17. Explain how the interactions between the T-Cell CD28 and APC differ from the interactions of TCell CD152 and APC-SKIP 18. Identify the Drugs a. Prednisone b. Prednisolone c. Methylprednisolone d. Dexamethasone as being Glucocorticoids 19. Explain the metabolic relationship between Prednisone and Prednisolone Prednisone is a parent molecule and metabolize in the liver to prednisolone (which is a little bit more active, it would be use if you have hepatic dysfunction) 20. Explain the mechanism of action of the Glucocorticoids as immunosuppressants 1.Lipocortin-1 inhibits the action of phospholipase A2 (responsible for releasing arachidonic acid from the membrane( pro inflammatory iseconoice) 2.Inhibits the formation of cytokines ( specially IL-2 which is most crucial effect in immunosuppression ,result in inhibition of T cell prefoliation and activation) .3.Also inhibits some B cell activity 21. Identify the Drugs a. Tacrolimus (PROGRAF) b. Cyclosporine (GENGRAF) as Calcineurin Inhibitors Asal Ardalan 22. Explain the mechanism of action of Calcineurin Inhibitors as immunosuppressants Cyclosporine (A) and tacrolimus are both antibiotics and they both bind to immunophilins. Cyclophilin is bound by cyclosporin and FKBP-12 is bound by tacrolimus, they both are immunophilins but they are different form . Once they bound they inhibit the action of calcineurin and it can’t dephosphorylate , it means it can’t enter the nucleolus and acts as a transcription factor to produce cytokines like IL-2 23. Identify Tacrolimus and Cyclosporine as highly lipophilic molecules Cyclosporine Tacrolimus 24. Explain why Tacrolimus has a volume of distribution (VD) of 1 L/kg based on blood, but 30 L/kg based on plasma-SKIP- goes in red blood cell 25. Identify the principal toxicity of the Calcineurin Inhibitors Nephrotoxicity is the limiting toxicity 26. Identify the enzyme primarily responsible for metabolism of Tacrolimus and Cyclosporine Cytochrome P3A(CYP 3A) 27. Identify the Drugs -Just know all of them are antiproliferative and antimetabolic drugs a. Sirolimus (RAPAMUNE) b. Everolimus (AFINITOR) c. Azathioprine (IMURAN)-Purine d. Mycophenolate Mofetil (CELLCEPT) e. Fingolimod (GILENYA) f. Terifluomide (AUBAGIO)-pyrimidine As Antiproliferative and Antimetabolic Drugs 28. For each of the drugs in question 27, describe the mechanism of action Asal Ardalan EXAM-Tacrolimus binds to FKBP-12( immunophilin) and to sirolimus also binds to FKBP-12 but doesn’t have the same MOA. Tacrolimus inhibits calciurine. Sirolimus inhibits mTOR enzyme (kinase, means it adds a phosphate to a molecule) Calciurine is a phosphatase , means it dephosphorylate things . Everolimus is same as sirolimus. Azathioprine(prodrug-purine): A purine antimetabolite. Converted in the body to 6mercaptopurine (active agent), they inhibit the synthesis of purine (inhibit the development of the cell-cause the death of the cell). Azathioprine metabolite interphase with the metabolize of T cell. Other side effects are increased susceptibility to infections, increased risk of neoplasia, hepatic and GI toxicity Pyrimidines are a single ring and purines are2 fused rings ( 6 or 5 rings ) 29. Identify the metabolic relationship between Azathioprine and 6-mercaptopurine( metabolite of azathioprine Asal Ardalan 30. Identify the primary toxicity of Azathioprine Major toxicity is bone marrow suppression 31. Identify the metabolic relationship between Mycophenolate Mofetil (MMF)is a prodrug and it’s an ester. Hydrolase in the body in the active form which is the acid Mycophenolic Acid (MPA) 32. Identify the other immunosuppressant drug that can delay elimination of MMF by immparing the conversion of MPA to its glucuronide metabolite (MPAG) 33. Identify the Drugs a. Muromonab-CD3 (ORTHOCLONE) b. Daclizumab (ZINBRYTA) c. Basiliximab (SIMULECT) d. Alemtuzumab (LEMTRADA) e. Belimumab (BENLYSTA) f. Rituximab (RITUXAN) g. Ocrelizumab (OCREVUS) h. Infliximab (REMICADE) i. Adalimumab (HUMIRA) j. Golimumab (SIMPONI) k. Certolizumab pegol (CIMZIA) l. Canakinumab (ILARIS) m. Natalizumab (TYSABRI) as mono clonal antibodies (MABs)-ANY DRUGS ENDING IN MAB is MABs 34. Recognize the drug Belatacept (NULOJIX) as a Fusion Protein that binds to cell surface costimulatory ligands CD80 and CD86 on APCs Belatacept is a selective T-lymphocyte costimulation blocker 35. Identify Glatiramer Acetate (COPAXONE) as a synthetic polypeptide that resembles myelin basic protein and inhibits T-Cell response to myelin antigens-SKIP 36. Define the following abbreviations-NOT IN THE EXAM a. APC - Antigen Presenting Cell b. CD - Cluster of Differentiation c. CTL - Cytotoxic Lymphocyte d. CTLA - Cytotoxic T-lymphocyte Associated Antigen e. FKBP - FK 506 Binding Protein f. HLA - Human Leukocyte Antigen g. IL - Interleukin h. MAPK - Mitogen Activated Protein Kinase i. MHC - Major Histocompatibility Complex j. MMF - Mycophenolate mofetill k. mTOR - Mechanistic Target of Rapamycin l. NFAT - Nuclear Factor of Activated T-Cells m. NF-κB - Nuclear Factor Kappa B n. NK cells – Natural Killer Cell o. NODAT - New Onset Diabetes Mellitus after Transplantation Asal Ardalan p. PD - Programmed Cell Death Protein q. TCR - T-cell Receptor r. TGF-β - Tumor Growth Factor Beta